This research project investigates the molecular mechanisms in the production of fever in humans. The experiments are designed to study the small molecular weight protein, leukocytic pyrogen (LP), which mediates fever. Areas of specific interest are: 1. the production of P from human cells, 2. physical characterization and purification of LP, 3. mechanisms of LP's action; and 4. detection of circulating LP in humans. These studies have provided new and significant information concerning the pathogenesis of fever in humans. Production of a human lymphokine from the mixed leukocyte reaction (MLR) opens an area of research on human immune fever in autoimmune diseases, drug allergies and other related immunological diseases. The initial studies on LP from neonatal phagocytic cells also may explain mechanisms involved in the failure in human infants to have fever when infected. This area is yet to be investigated. These studies on the mechanism of action of human LP in mediating the acute-phase responses adds vital new data on associated, non-specific data changes induced by many infectious and inflammatory diseases. Our studies on physical configuration of the LP molecule necessary for the production of fever provides needed information about the molecular mechanism of fever. This data will enable further experimentation on the subcellular level for the production of fever. Combined with the above data, our abblity to measure levels of LP in patients during fever provides important new information for the pathogenesis of fever in humans.